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The removal of activated HSCs has a reversal effect on liver fibrosis. Western blot and MTT analysis indicated that curcumol could relieve hepatic fibrosis by promoting HSCs receptor\u2010interacting protein kinase 1\/3 (RIP1\/RIP3)\u2010dependent necroptosis. Importantly, autophagy flow was monitored by constructing the mRFP\u2010GFP\u2010LC3 plasmid, and it was found that curcumol cleared activated HSCs in a necroptosis manner that was dependent on autophagy. Our study suggested that the activation of necrosome formed by RIP1 and RIP3 depended on Atg5, and that autophagosomes were also necessary for curcumol\u2010induced necroptosis. Furthermore, microscale thermophoresis and co\u2010immunoprecipitation assay results proved that curcumol could target Sirt1 to regulate autophagy by reducing the acetylation level of Atg5. The HSCs\u2010specific silencing of Sirt1 exacerbated CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced liver fibrosis in mice. The deacetylation of Atg5 not only accelerated the accumulation of autophagosomes but also enhanced the interaction between Atg5 and RIP1\/RIP3 to induce necroptosis. Overall, our study indicated that curcumol could activate Sirt1 to promote Atg5 deacetylation and enhanced its protein\u2013protein interaction function, thereby inducing autophagy and promoting the necroptosis of HSCs to reduce liver fibrosis.\n                  <\/jats:p>","DOI":"10.1002\/ptr.7483","type":"journal-article","created":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T20:19:49Z","timestamp":1652300389000},"page":"2660-2676","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Modification of lysine deacetylation regulates curcumol\u2010induced necroptosis through autophagy in hepatic stellate cells"],"prefix":"10.1002","volume":"36","author":[{"given":"Sumin","family":"Sun","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing 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